Nonassociative learning processes determine expression and extinction of conditioned fear in mice

Kamprath, Kornelia; Wotjak, Carsten T.

doi:10.1101/lm.86104

Cited by 169 publications

(160 citation statements)

References 42 publications

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“…There are a number of respects in which the 'sensitization' phenomenon reported by Kamprath et al 55,237 runs counter to what would be expected based on a classical conception of sensitization. For example, sensitized freezing occurs even at a long delay after footshock exposure (in one case, as long as 1 month 237 ), and is mitigated by pre-exposure to the tone before footshock, a phenomenon reminiscent of latent inhibition.…”

Section: Neurotransmitter Systemsmentioning

confidence: 73%

“…A number of commonalities between habituation and extinction have been noted and used as the basis for an argument that the response decrement in both cases may arise at least partly through the same mechanism. [54][55][56][57] In the framework of associative theory, this sort of mechanism may be translated in terms of the degree to which the CS and/or US representations can be activated (Figure 2d -cf. Wagner 53 ).…”

Section: New Learningmentioning

confidence: 99%

“…That is, endogenous cannabinoid release is not a mechanism of fear extinction per se but rather occurs under conditions in which habituation occurs, which include, but are not specific to, extinction. The argument that extinction involves a significant habituation component is one that has been raised by several authors 54,56,57 (discussed earlier) and most recently was put forward by Kamprath and Wotjak, 55 who in a series of experiments demonstrated that mice exhibit freezing to a tone not only following tone-footshock pairings but also following exposure to footshock alone. In these experiments, mice were presented with one or more footshocks in a distinctive experimental context, then subsequently were placed into a different context and presented with a tone.…”

Section: Neurotransmitter Systemsmentioning

confidence: 99%

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Mechanisms of fear extinction

2006

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Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications. Molecular Psychiatry (2007) 12, 120-150.

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Section: Neurotransmitter Systemsmentioning

confidence: 73%

Section: New Learningmentioning

confidence: 99%

Section: Neurotransmitter Systemsmentioning

confidence: 99%

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Mechanisms of fear extinction

2006

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“…What is unknown is whether this vestige is associative or nonassociative. Although CFC is associative in nature (Fanselow 1986;Sauerhöfer et al 2012), fear conditioning in mice can also produce significant nonassociative behavioral plasticity, which is evidenced by increases in anxiety-like behavior and the display of fear in response to cues never paired with shock (Kamprath and Wotjak 2004). Thus, the presence of savings after extinction does not definitively demonstrate preservation of the original context-US association, as savings could reflect nonassociative plasticity.…”

Section: Discussionmentioning

confidence: 90%

Potent attenuation of context fear by extinction training contiguous with acquisition

Bernier

Lacagnina

Drew³

2014

Learn. Mem.

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Studies on the behavioral mechanisms underlying contextual fear conditioning (CFC) have demonstrated the importance of preshock context exposure in the formation of aversive context memories. However, there has been comparatively little investigation of the effects of context exposure immediately after the shock. Some models predict that nonreinforced context exposure at the end of the acquisition session will strongly influence the strength of conditioning and/or recruit distinct neural mechanisms relative to extinction after acquisition. Here we investigate the effects of manipulating postshock context exposure on CFC in mice. Prolonging the period of context exposure immediately following the shock caused a significant and durable reduction in conditioned fear. This immediate postshock context exposure was more effective at attenuating conditioned fear than was an equivalent amount of context exposure a day or more after acquisition. The results suggest that nonreinforced exposure to the context influences conditioned fear through distinct mechanisms depending on whether it occurs during acquisition or after it. The superiority of immediate postshock context exposure was specific to single-shock CFC; in two-shock CFC, immediate and delayed postshock context exposure had similar effects. Consistent with previous reports, we hypothesize that the effectiveness of extinction is modulated by emotional state, and procedures engendering higher postshock freezing (such as two-shock CFC) are associated with weaker immediate extinction.Contextual fear conditioning (CFC) is a form of associative learning that occurs when an aversive experience, usually a footshock in laboratory experiments, occurs within a distinctive place or context. Learned contextual fear typically recruits plasticity in the hippocampus, which is thought to generate a conjunctive mnemonic representation of stimuli present during the learning episode (Rudy et al. 2004;Fanselow 2010). The robustness of this form of learning has made it one of the preferred methods for studying mechanisms of hippocampus-dependent memory and learned fear.While the neural mechanisms of CFC have been researched extensively, there has been comparatively little investigation of the behavioral mechanisms through which the emotional valence of a context is established. One longstanding idea is that the strength of context conditioning is determined by the overall rate of unconditioned stimulus (US) presentation per unit time in the context (Rescorla and Wagner 1972;Gibbon and Balsam 1981). This approach accounts for the observation that increasing the intertrial interval in conditioning experiments tends to decrease the amount of conditioned responding elicited by the context (Fanselow et al. 1993;Barela 1999). However, this model fails to account for a key property of CFC: very brief preshock context exposure leads to an absence of context fear, rather than robust fear as the rate-based model would predict (Fanselow 1986). This phenomenon, known as the immediate shock defici...

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“…This indicates that rBDNF does not affect the hippocampal-dependent processes that mediate the retrieval of CFM (Fanselow 2000), or the habituation of conditioned fear responses (Kamprath and Wotjak 2004). The impairment of extinction by rBDNF was both rapid and sustained because freezing behavior was comparable to rats that had not undergone extinction training (short recall group) at the earliest postretrieval test (PR-STM) 3 h later and at long-term retrieval tests for at least 21 d. This shows that increasing mBDNF in the hippocampus around the time of a nonreinforced trial impairs the acquisition of the extinction of CFM.…”

Section: Discussionmentioning

confidence: 99%

The exclusive induction of extinction is gated by BDNF

Kirtley¹,

Thomas²

2010

Learn. Mem.

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We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268 activity in this region. Here we show that by infusing a recombinant brain-derived neurotrophic factor (rBDNF) directly into the brain of rats, that high levels of mature BDNF in the hippocampus at retrieval constrain the extinction of the fear memory after prolonged memory recall. We also show after a short CS exposure that reconsolidation was impaired using antisense oligonucleotides targeting Zif268, and that, similarly, reductions in conditioned behavior were observed after prolonged CS presentation when extinction is constrained by high levels of BDNF. This is direct evidence that in the mammalian brain extinction proceeds exclusively after prolonged CS exposure. In addition, that BDNF activity in the hippocampus contributes to a molecular switch for the extinction of hippocampal-dependent memory.

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Nonassociative learning processes determine expression and extinction of conditioned fear in mice

Cited by 169 publications

References 42 publications

Mechanisms of fear extinction

Mechanisms of fear extinction

Potent attenuation of context fear by extinction training contiguous with acquisition

The exclusive induction of extinction is gated by BDNF

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